374TiP - LAURA: Osimertinib maintenance following definitive chemoradiation therapy (CRT) in patients (pts) with unresectable stage III epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC)

Background

Platinum-based CRT followed by durvalumab consolidation (PACIFIC study regimen) is standard of care for pts with unresectable Stage III NSCLC, without progression after platinum-based CRT. In PACIFIC, only 6% of pts had EGFRm NSCLC. Osimertinib is a 3rd-generation, CNS-active, oral, irreversible EGFR tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations. FLAURA data (median OS: HR 0.80; 95.05% CI 0.64, 1.00; P=0.046) indicate osimertinib could provide benefit to pts with unresectable Stage III NSCLC. LAURA (NCT03521154) will assess the efficacy and safety of osimertinib as maintenance therapy in pts with locally advanced, unresectable, EGFRm, Stage III NSCLC without disease progression during/following definitive platinum-based CRT. Previously presented: WCLC, Shun L et al. 2018 J Thorac Oncol;13(10 suppl):S497; we report protocol updates (Feb 2020).

Trial design

In this Ph III, double blind, placebo-controlled trial, pts will be randomized (2:1) to osimertinib 80 mg/day or placebo, until objective radiological disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, confirmed by blinded independent central review (BICR). Key inclusion criteria: ≥18 years (≥20 Japan); locally advanced unresectable Stage III NSCLC; central/local confirmation of Ex19del/L858R; WHO PS 0–1; ≥2 cycles of concurrent/sequential platinum-based CRT; no investigator-assessed (IA) progression; creatinine <1.5x ULN and creatinine clearance ≥30 mL/min. Primary objective: to assess the efficacy of osimertinib by BICR progression-free survival (PFS). Secondary objectives: PFS by mutation status, CNS PFS, OS and safety. Pts with BICR-confirmed disease progression (IA-confirmed if after PFS analysis) may be un-blinded to receive open-label osimertinib; all will have post-progression follow-up. Serious adverse events (SAEs) and AEs of special interest will be collected throughout the study and survival follow-up. First pt enrolled July 2018; results expected late 2022.

Clinical trial identification

NCT03521154.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S. Lu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Hutchison MediPharma; Advisory/Consultancy: Simcere; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Advisory/Consultancy: GenomiCare; Research grant/Funding (self): Hutchison; Research grant/Funding (self): Bristol Myers Squibb; Research grant/Funding (self): Heng Rui; Speaker Bureau/Expert testimony: Hansoh. T. Kato: Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Biopharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ono; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Nippon Kayaku; Advisory/Consultancy: Nitto Denko; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Chugai; Speaker Bureau/Expert testimony: Taiho, Daiichi-Sankyo, F. Hoffmann-La Roche, Shionogi, Sumitomo Dainippon; Licensing/Royalties: Astellas, Kyorin, Kyowa-Kirin, Regeneron; Research grant/Funding (self), Personal fees: AstraZeneca. M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Astellas; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Roche. L. Zeng: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. T. van der Gronde, M. Saggese: Full/Part-time employment: AstraZeneca. S. Ramalingam: Advisory/Consultancy, Research grant/Funding (self): Amgen; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): Tesaro; Advisory/Consultancy, Research grant/Funding (self): Takeda; Research grant/Funding (self): Advaxis; Research grant/Funding (self): Genmab. All other authors have declared no conflicts of interest.